Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas.
Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas.
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发表时间：
2002-04
期刊：
影响因子：
11.2
通讯作者：
D. Gutmann;N. Hedrick;Jun Li;R. Nagarajan;A. Perry;M. Watson
中科院分区：
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作者：
D. Gutmann;N. Hedrick;Jun Li;R. Nagarajan;A. Perry;M. Watson
毛细胞性星形细胞瘤 (PA) 是 WHO I 级脑肿瘤，通常不会进展为更恶性的星形细胞瘤。尽管高级别星形细胞瘤的分子遗传学取得了重大进展，但人们对与 PA 形成相关的遗传变化知之甚少。为了更好地表征这些低度肿瘤，我们将六种散发性和两种神经纤维瘤病 1 相关 PA 的基因表达谱与星形胶质细胞和少突胶质细胞来源的其他组织和细胞系进行了比较。基因表达数据的层次聚类分析清楚地描绘了来自低度少突胶质细胞瘤和正常白质的 PA。两个 NF1 相关肿瘤和一个散发的 PA 显示的表达谱与培养的正常人胎儿星形胶质细胞的表达谱更密切相关。然而，PA 还表达通常与少突胶质细胞谱系相关的单个基因（例如蛋白脂质蛋白和 PMP-22）。特定基因（例如 ApoD）的表达模式是 PA 肿瘤所独有的，而高级别星形细胞瘤的遗传变化特征并未遇到。两种转录物（神经细胞粘附分子和连接蛋白-43）的差异表达在蛋白质水平得到证实，表明这些细胞粘附分子可能在这些肿瘤的分子发病机制中特别重要。我们得出的结论是，PA 是遗传上独特的神经胶质瘤，其基因表达谱类似于胎儿星形胶质细胞，并且在较小程度上类似于少突胶质细胞前体。
Pilocytic astrocytomas (PAs) are WHO grade I brain tumors that do not typically progress to more malignant grades of astrocytoma. Whereas there have been significant advances in the molecular genetics of high-grade astrocytomas, relatively little is known about the genetic changes associated with PA formation. In an effort to better characterize these low-grade neoplasms, we compared the gene expression profiles of six sporadic and two neurofibromatosis 1-associated PAs with other tissues and cell lines of both astrocytic and oligodendroglial origin. Hierarchical cluster analysis of gene expression data clearly delineated PAs from low-grade oligodendrogliomas and normal white matter. The two NF1-associated tumors and one of the sporadic PAs displayed expression profiles that were more closely related to those of cultured normal human fetal astrocytes. However, PAs also expressed individual genes typically associated with oligodendroglial lineage (e.g., proteolipid protein and PMP-22). The expression patterns of specific genes (e.g., ApoD) were unique to PA tumors, whereas genetic changes characteristic of high-grade astrocytomas were not encountered. Differential expression of two transcripts, neural cellular adhesion molecule and connexin-43, was confirmed at the protein level, suggesting that these cell adhesion molecules might be particularly important in the molecular pathogenesis of these tumors. We conclude that PAs are genetically unique gliomas with gene expression profiles that resemble those of fetal astrocytes and, to a lesser extent, oligodendroglial precursors.